In response to RFA-DA-05-007, we propose a 5-year cross sectional investigation with a one-year prospective follow-up to further our understanding of the neurobiological consequences of an adolescent onset cannabis use disorders (CUD; defined as DSM-IV cannabis dependence or abuse) on adolescent prefrontal and hippocampal structural and functional development. We propose to measure prefrontal and hippocampal cognitive function with a comprehensive neuropsychological battery and a functional MRI (fMRI) scan aimed at measuring subdivisions of prefrontal cortex (RFC) involved in decision-making and reward. We hypothesize that adolescent CUD will be associated with deficits of prefrontal and hippocampal function. Three adolescent groups will be compared: 1) adolescents with CUD, who do not have other comorbid substance use disorders (SUDs) and who are entering intensive substance treatment, 2) a high risk for SUD group of adolescents with mental disorders who do not have any SUDs and are age, sex, and sociodemographically matched to the CUD subjects, and 3) age, sex, and sociodemographically matched healthy community control adolescents. Specific aims are to compare measures of prefrontal and hippocampal structure and function in adolescents with CUD at baseline and prefrontal and hippocampal neuropsychological function at baseline, and 6 and 12 month follow-ups. At baseline, a well characterized subsample will undergo a novel fMRI task to measure RFC activity. We will explore the relationship between baseline measures of RFC activity in all adolescent groups to examine factors associated with: 1) nonremission or progression to other SUDs in the adolescent CUD group; and 2) emergence of an adolescent onset CUD in the high risk and healthy control groups; at 6 and 12 months. We will explore clinical summary variable measures of the subject's remission of cannabis use (age of onset of remission, duration of remission) and presence of mental health co-morbidity to try to identify the best clinical predictors of neuropsychological function (e.g. improvement) at 6 and 12 months. The adolescent brain is more vulnerable to the effects of drug abuse than the adult brain. This proposal has public health significance because we will comprehensively evaluate the effects of marijuana on adolescent brain and cognitive development, an understudied area.